No evidence for cholinergic problems in apolipoprotein E knockout and apolipoprotein E4 transgenic mice

The epsilon 4 allele of the apolipoprotein E gene constitutes the major gen etic risk factor to develop Alzheimer's disease. If and how this protein co ntributes to the pathological cascade of Alzheimer's disease is not known. The epsilon 4 allele particularly affects the cholinergic defect, which is one of the most consistent neurotransmitter problems in an Alzheimer's dise ase brain. We have analysed several parameters of the cholinergic system in brain of a polipoprotein E knockout mice as well as in transgenic mice overexpressing human apolipoprotein E4. We analysed the distribution of cholinergic fibers , the number and morphology of cholinergic neurons and the enzymatic activi ty of acetylcholinesterase and choline acetyltransferase in different brain regions. Finally, we analysed the distribution and the binding parameters of [H-3]hemicholinium-3, a specific marker for the high affinity choline tr ansporter in different brain sections and regions. This extensive effort failed to show any consistent difference in the choli nergic parameters studied, in either the apolipoprotein E4 transgenic mice or in the apolipoprotein E knockout mice, compared to age-matched non-trans genic mice. We conclude that the apolipoprotein E4 is not deleterious per s e for the cholinergic system in mouse brain. (C) 2000 IBRO. Published by El sevier Science Ltd.